7
October 6, 2009 Worsening fever and chills New onset chest pain and left arm numbness Decreased grip strength of left hand EKG showed no signs of cardiac ischemia Asked to return the following day Advised to seek medical attention if symptoms worsened

8
October 6, 2009 Presented to a local Emergency Department Chest and back pain described as “spasm” Evaluation similarly unremarkable Cardiac ischemia and pulmonary embolus ruled out Prescribed narcotics and muscle relaxants for presumed musculoskeletal pain

9
October 7, 2009 Returned to same Emergency Department Worsening pain and back spasms Akathisia and motor restlessness attributed to side effects of muscle relaxant Hospital admission advised but the patient returned home

12
October 20, 2009 Brain death was diagnosed based on physical examination, electroencephalogram, and apnea testing Ventilatory support withdrawn and patient died

13
Differential Diagnosis Rabies thought unlikely given the absence of animal exposure One day prior to the patient’s death – CDC contacted for consultation – Antemortem samples submitted for diagnostic testing

14
Preliminary Results Rabies specific antibodies in serum Diagnosis expected to be confirmed at autopsy Pathologists concerned about the biosafety risks of performing an autopsy on a patient with suspected rabies – Infectious aerosols – Contamination of autopsy facilities

22
Public Health Response 18 potential exposures identified – 14 healthcare providers, 2 family members, and 2 coworkers All 18 were recommended to receive PEP and all completed the vaccination series To date, none of the 159 persons has developed rabies

23
Public Health Response No specific source of rabies virus exposure Mechanic in a rural farming community in southern Indiana Mentioned seeing a bat after removing a tarpaulin from a tractor Never reported a bite or nonbite exposure

34
CSTE Definition of Human Rabies Confirmed - a clinically compatible case that is laboratory confirmed Clinical description – Rabies is an acute encephalomyelitis that almost always progresses to coma or death within 10 days after the first symptom.

35
CSTE Definition of Human Rabies Laboratory criteria for diagnosis – Detection by direct fluorescent antibody of viral antigens in a clinical specimen (preferably the brain or the nerves surrounding hair follicles in the nape of the neck), OR – Isolation (in cell culture or in a laboratory animal) of rabies virus from saliva, cerebrospinal fluid (CSF), or central nervous system tissue, OR – Identification of a rabies-neutralizing antibody titer greater than or equal to 5 (complete neutralization) in CSF – Identification of a rabies-neutralizing antibody titer greater than or equal to 5 (complete neutralization) in the serum of an unvaccinated person.

36
Proposed New Case Definition Laboratory criteria for diagnosis – Detection by direct fluorescent antibody of lyssavirus antigens in a clinical specimen (preferably the brain or the nerves surrounding hair follicles in the nape of the neck), OR – Isolation (in cell culture or in a laboratory animal) of a lyssavirus from saliva or central nervous system tissue, OR – Detection of lyssavirus RNA (using reverse transcriptase- polymerase chain reaction [RT-PCR]) in saliva, CSF, or tissue, OR – Identification of a rabies-binding antibody in the CSF, OR – Identification of a rabies-binding antibody titer in the person’s serum AND no history of rabies vaccination

37
ACIP Definition of Rabies Exposure Bite exposure – most common and most dangerous route of exposure – Bite from a rabid mammal Nonbite exposure – lower risk – The introduction of rabies virus (from saliva or other potentially infectious material, e.g.,neural tissue) into fresh, open cuts in skin or onto mucous membranes Postexposure prophylaxis should be administered for either type of exposure

38
ACIP Definition of Rabies Exposure Indirect contact and activities such as petting or handling an animal, contact with blood, urine or feces, and contact of saliva with intact skin do not constitute exposures These situations do not require administration of postexposure prophylaxis

41
Aerosol Transmission of Rabies 1972: 56y/o veterinarian died of rabies 2 weeks after homogenizing rabid goat brain using a blender known to produce a lingering aerosol – It is believed that he removed his mask to do mouth pipetting of aliquots of the homogenate, raising the question of mucous membrane exposure

42
Aerosol Transmission of Rabies 1977: 32y/o lab technician became ill after spraying suspensions of a modified live rabies virus in a pharmaceutical manufacturing machine – The patient did not die but was left with severe neurologic sequelae – The diagnosis was based on his neurologic symptoms and rising rabies Ab titers – It is hypothesized that the virus involved had developed higher infectivity after passing through animal and tissue culture systems

43
Aerosol Transmission of Rabies 1956: Entomologist studying the ecology of bats died of rabies after visiting several caves in central Texas – Death often attributed to aerosol transmission – However, it was also reported that he had a chronic skin eruption on his neck and that he scratched or rubbed it while wearing the same gloves he used to handle the bats – Raises the question of introduction of virus into the wound

44
Aerosol Transmission of Rabies 1959: Mining engineer who frequented caves to evaluate them for guano mining and had visited a cave one month before the onset of symptoms – One history states that he denied any bat bites but had a bleeding lesion on his face when leaving the cave – Another states he was bitten but then later denied it – In either case, the bleeding lesions raises the question of introduction of virus into the wound

45
Human-Human Rabies Transmission Organ and tissue transplantation resulting in rabies transmission has occurred among 16 transplant recipients Theoretically, human-to-human transmission could also occur in the same way as animal- to-human transmission No laboratory-diagnosed cases of human-to- human rabies transmission have been documented other than the transplant cases

50
New Recommendations Use personal protective equipment, including an N95 or higher respirator, full face shield, goggles, and gloves, as well as complete body coverage with protective wear Use heavy or chain mail gloves to help prevent cuts or sticks from cutting instruments or bone fragments

51
New Recommendations Minimize aerosol generation by using a handsaw rather than an oscillating saw and avoiding contact of the saw blade with brain tissue while removing the calvarium Limit participation to those directly involved in the procedure and collection of specimens

52
New Recommendations Use ample amounts of a 10% sodium hypochlorite solution during and after the procedure to ensure decontamination of all exposed surfaces and equipment

53
New Recommendations Previous vaccination against rabies is not required for persons performing such autopsies, and postexposure prophylaxis of autopsy personnel is recommended only if contamination of a wound or mucous membrane with patient saliva or other potentially infectious material (e.g., neural tissue) occurs during the procedure